Inherited nongenetic influences on the gut microbiome and immune system.

The gut microbiome and the immune system codevelop around the time of birth, well after genetic information has been passed from the parents to the offspring. Each of these "organ systems" displays plasticity. The immune system can mount highly specific adaptive responses to newly encountered antigens, and the gut microbiota is affected by changes in the environment. Despite this plasticity, there is a growing appreciation that these organ systems, once established, are remarkably stable. In health, the immune system rapidly mounts responses to infections, and once cleared, resolves inflammatory responses to return to homeostasis. However, a skewed immune system, such as seen in allergy, does not easily return to homeostasis. Allergic responses are often seen to multiple antigens. Likewise, a dysbiotic gut microbiota is seen in multiple diseases. Attempts to reset the gut microbiota as a therapy for disease have met with varied success. Therefore, how these codeveloping "organ systems" become established is a central question relevant to our overall health. Recent observations suggest that maternal factors encountered both in utero and after birth can directly or indirectly impact the development of the offspring's gut microbiome and immune system. Here, we discuss how these nongenetic maternal influences can have long-term effects on the progeny's health.